Role of a New Mammalian Gene Family in the Biosynthesis of Very Long Chain Fatty Acids and Sphingolipids

Abstract

Whereas the physiological significance of microsomal fatty acid elongation is generally appreciated, its molecular nature is poorly understood. Here, we describe tissue-specific regulation of a novel mouse gene family encoding components implicated in the synthesis of very long chain fatty acids. The Ssc1 gene appears to be ubiquitously expressed, whereas Ssc2 and Cig30 show a restricted expression pattern. Their translation products are all integral membrane proteins with five putative transmembrane domains. By complementing the homologous yeast mutants, we found that Ssc1 could rescue normal sphingolipid synthesis in the sur4/elo3 mutant lacking the ability to synthesize cerotic acid (C26:0). Similarly, Cig30 reverted the phenotype of the fen1/elo2 mutant that has reduced levels of fatty acids in the C20–C24 range. Further, we show that Ssc1 mRNA levels were markedly decreased in the brains of myelin-deficient mouse mutants known to have very low fatty acid chain elongation activity. Conversely, the dramatic induction of Cig30 expression during brown fat recruitment coincided with elevated elongation activity. Our results strongly implicate this new mammalian gene family in tissue-specific synthesis of very long chain fatty acids and sphingolipids.

Evidence that oestrogen receptor-α plays an important role in the regulation of glucose homeostasis in mice: insulin sensitivity in the liver

“…Elov13 is necessary for the synthesis of very-long-chain fatty acids. Changes in the expression of Elovl3 may lead to membrane defects, including the modification of phospholipid composition and signal transduction [38]. On the other hand, expression of Sth2 (steroid metabolism pathway) was markedly decreased.…”

ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

“…For Elovl1 and Elovl3, an NheI-site in the reported constructs [5,22] was modified to the NotI-site, and each cDNA flanked by two NotIsites isolated by NotI. For Elovl2, a cDNA in pEMR1023 [8] was excised by SalI and BglII, and both ends converted to NotI-sites. The Elovl1-3 cDNA fragments obtained were ligated to modified pCXN2 as above.…”

“…For Elovl1 and Elovl3, constructs in pCIneo [5,21] were used. For Elovl2, a cDNA in pEMR1023 [8] was subcloned into pGemT. For diacylglycerol acyl transferase (DGAT)2 and fatty acid synthase (FAS), two expressed sequence tag clones (IMAGE5123807 and IMAGE4195432) were used.…”

“…Seven ELOVL members have been identified in mice and humans, each having a respective gene locus, a unique tissue specific expression pattern with overlapping substrate specificity [5][6][7][8]. Saturated and monounsaturated FAs are preferred substrates of ELOVL1, ELOVL3 and ELOVL6 [8][9][10][11], whereas ELOVL2, ELOVL4 and ELOVL5 use polyunsaturated fatty acids (PUFAs) primarily [10,12,13].…”

“…Saturated and monounsaturated FAs are preferred substrates of ELOVL1, ELOVL3 and ELOVL6 [8][9][10][11], whereas ELOVL2, ELOVL4 and ELOVL5 use polyunsaturated fatty acids (PUFAs) primarily [10,12,13].…”